Innate control of virus infections at epithelial surfaces - novel mechanisms

Many viral infections utilizes epithelial surfaces as the portal of entry into the body of the host. Hence mucosal surfaces are frequently exposed to viruses and represent a first line of defense.

The current dogma in immunology is that pattern recognition receptors (PRR) mediate activation of the first line of innate defense.

However, PRRs induce potent immune responses, often associated with immunopathology – in addition to antimicrobial activity.

I previously reported antiviral mechanisms operating on epithelial surfaces independent of PRRs and the canonical interferon system (Nat Immunol 17:150), and recently proposed a conceptual framework for this phenomenon (Nat Rev Immunol, 2021).

Here I will use genome-wide screening tools, state-of-the-art molecular/cellular systems, and animal models to identify and characterize two suggested novel pathways in antiviral defense.

The proposal is founded on solid preliminary data, the project group is established, and key reagents/methodologies are in place.

The project will challenge the current dogma in innate immunology, and will contribute with ground-breaking new understanding of how infections are eliminated at epithelial surfaces in a subclinical manner.